Estradiol from the ovary and follicle stimulating hormone (FSH) from the pituitary are required for follicle growth. However, the mechanisms whereby these hormones control ovarian function are unknown. The major objective of this proposal is to determine how estradiol regulates the ability of FSH to increase FSH receptors in developing ovarian follicles. Regulation of FSH receptors in the follicle appears to be the most important limiting factor for follicular growth. Six experiments are proposed (I, II, III, IV, V, VI). Experiment I is designed to determine when increases in 125I-hFSH binding to granulosa cell membranes occur and, by comparison, when increases in estradiol receptor in the nucleus occur following hFSH treatment. Experiment II will attempt to determine if the increase in specific binding of 125I-hFSH to granulosa cells following injections of hFSH is coupled in some manner with a stimulation of endogenous estradiol production. Experiment III is designed to determine if estradiol enhancement of the ability of FSH to increase FSH receptor requires cell divisions and/or cell differentiation. In Experiment IV, I will examine the effects of estradiol on the ability of FSH to stimulate cAMP accumulation in follicles. In Experiment V, I will determine the effects of estradiol on FSH responsive adenylate cyclase activity. Experiment VI is designed to determine if cAMP can mimic the effects of FSH on receptor content for FSH and LH in granulosa cells. The results of these studies should indicate if estradiol is required for FSH action, elucidate possible sites of estradiol action in the ovary, and provide further basic information as to how estradiol and FSH interact to control follicular development.